Genesis:Region Information
There are three main regions for Genesis/Mega Drive hardware; Japanese, US and Europe/PAL. All of these regions are determined by two pins on the VDP or main ASIC, one for language (English/Japanese) and the other for video frequency (50/60 Hz). Each pin is set by either connecting them high (5V) or low (ground). Most games released before 1993 largely ignore these settings, but many released after this period perform a check to determine which console the game is running on. If the game detects a mismatch between what it expects and the console's region settings, it will not boot and often times will display a warning message (i.e. "Developed For Use Only with NTSC Genesis Systems."). Most Sega/Mega CD systems also perform this region check in their BIOS, and it cannot be bypassed without performing a region mod on the Genesis/Mega Drive console or replacing the BIOS on the CD hardware with a region-free one. Loading a region-free BIOS via a flash cart will also work.
Unlike its predecessor, the Genesis/Mega Drive uses the exact same cartridge pinout and connector across all regions.
For more information, consult the region coding page on Sega Retro, which also includes an exhaustive list of games which are region locked or function differently depending on region.
Asian/Japanese/Korean
Japanese and Korean consoles have the language pin held low (JP) and the video frequency pin held high (60 Hz). Asian market consoles are largely the same as their Japanese counterparts but run at 50 Hz as many Asian countries use PAL. One important note about Japanese cartridges is that they have a different shape than Western cartridges, and will not fit in a Genesis or European Mega Drive without physically modifying the console shell or using an adapter. Asia and Korea also used this same cartridge shape.
US and PAL cartridges will easily fit into a Japanese Mega Drive with room to spare, but they lack a cutout on the left side for the model 1 console's cartridge lock, preventing the console from powering on. This can be easily circumvented by removing the cartridge lock mechanism in the console's top shell, allowing the console to power on with a US/PAL cartridge inserted. As long as the cartridge does not check for region, they should play perfectly on a Japanese console. All other Japanese Mega Drive models lack the cartridge lock so US/PAL cartridges will fit without any issues.
North American/Brazilian
North American and Brazilian consoles have both the language and video frequency pins held high (EN, 60 Hz).
For the North American market, Sega changed the Japanese Mega Drive's cartridge shape to a slightly smaller one, which is rounded at the front and slightly squared off at the back. Most Genesis consoles have a cartridge slot which tightly follows this outline, preventing the thicker Japanese cartridges from fitting. The only two exceptions to this are the JVC X'Eye (which has a squared-off slot like its Japanese counterpart) and the Genesis 3; while the Genesis 3 can accommodate most Japanese cartridges, the slightly thicker cartridges used by Sunsoft will not fit.
Europe/PAL
PAL consoles have the language pin held high (EN) and the video frequency pin held low (50 Hz).
Sega also used the exact same cartridge shape as the US, so PAL games will fit without issue in a Genesis console and vice versa. As with the Genesis, Japanese cartridges will not fit in a PAL Mega Drive. Furthermore, PAL games which do not perform the region check will play perfectly fine on a Genesis, with a large number running at their intended speed since many PAL games were not optimized for 50 Hz. Conversely, Genesis games without the region check will play fine on a PAL Mega Drive, but may play at a slower than intended speed.
Notes about Cartridge Shapes
Despite the regional differences between cartridge shapes as described above, there are some notable exceptions. Electronic Arts and Accolade cartridges are narrower than official cartridges and these will fit into any region console. Sonic & Knuckles (which does not have a region check) and the 32X add-on follow the US/PAL cartridge outline but have a cutout in the side for the Japanese model 1. This may have been done as a cost-cutting move by Sega in order to avoid making unique cartridge molds for non-Western consoles.
In Japan, a few third party publishers opted to manufacture their own cartridges, such as Capcom, Konami, Namco, Sunsoft and Taito. Most of these publishers chose to follow the exact same shape as Sega-manufactured cartridge shells, but Sunsoft and Taito took some liberties with the design. Taito cartridges are slightly thicker and completely smooth at the sides, while Sunsoft went with thicker and squared-off sides. The Mega Adaptor, which is the Japanese version of the Power Base Converter, has a rectangular shape which fills in the entire cartridge slot on a Japanese Mega Drive.