No direct Mac support through the client itself
Website-only downloads of standalone Mac release installers are currently supported.
No game API
No game API ready yet, other than the Opt-In system to have the Desura server send developer's server user account information when the user Opts-In.
No Desura web profile/site customization
Game and mod sites are not fully customizable yet.
No support for standalone mods
Stand-alone modifications can't be installed unless Desura detects the original game. Those defined on ModDB as mods (not games) and standalone are e.g. Twisted Insurrection, Ya3dag, HoN 2 DotA.
Complex mods, such as those installing to the game main directory or overwriting original game files, are less/poorly supported
Desura works well with simple mods that can be installed to their own single mod folders. Unlike advanced mod managers, Desura is less suitable for complex mods requiring back-ups. Only a couple of "complex" modifications were published, such as Median XL, Max Payne 2 mods, and Circle of Eight. Usually only one complex mod can be published for a given game.
That's also why C&C Generals and Age of Empires III mods are still pending (these shouldn't be published). The current state is that such mods linger on Desura client download authorization list for more than 10 months (Oblivion mod Nehrim was uploaded there more than 1 year ago).
The client searches for games only in Documents/Users and Program Files folders and via specific Windows registry keys
If you have your games installed to e.g. C:\Games\, for example C:\Games\Fallout 2, you can experience problems trying to find this specific game through the client.
No support for mods installing to multiple folders
Mods such as modules for Neverwinter Nights can be hardly supported through Desura. Such modifications require simple install (copying/pasting) to multiple folders and completely different directories (both to Documents and Program Files/game folders), something that is currently completely unsupported by Desura. Linux Mods are poorly supported at this time and could be installed only to Desura or user (home/username) directory.
No separate install settings for different releases of the same mod/game
For example, minimods installing to folders different than the main mod release cannot be supported. An example of such minimod is Achilles minimod from RA3 Paradox mod profile.
(Only platform-based install settings are supported, Windows, Linux and Linux 64 bit have separate install settings.)
Links helpful for setting things up and understanding the Desura system
These links are from various Desura wiki pages and should help you get things setup for your game.