Some drug possession defenses can work well when you're trying to show why you had drugs that were either illegal or not prescribed to you. If you decide not to plead guilty, then you can fight the charges and hopefully reduce or eliminate them.
Drug possession defenses work best when you can appropriately challenge the facts, testimony, or evidence provided. You could also challenge procedural errors, defend yourself due to needing the drug in question for medical needs, or challenge charges based on search and seizure violations.
Search and seizure issues are some of the most common for the courts. Here's an example. If you have drugs tucked under your car's seat, the officer should not be able to search your vehicle or take those drugs without permission from you or a warrant. The officer must have a reason to believe you have violated the law in order to stop you, too.
You could also argue that the drugs belong to someone else. If you recently took friends with you to the beach, for example, and one of them had marijuana on hand that later got left behind, then you may be able to prove that you had no idea the drugs were in your vehicle and that they don't belong to you.
You can also defend yourself by proving the substance isn't what the police think it is. For example, white powder may look like cocaine, or glass-like crystals could look like methamphetamine. Looks can be deceiving; a lab analysis should always be performed to prove that the "drugs" are actually another substance altogether.
Source: FindLaw, "Drug Possession Defenses," accessed May. 19, 2015