As the use of cannabis increases, there is a need to identify appropriate analytical methods that are sensitive in measuring cannabinoid compounds and their metabolites. This chapter offers an overview of the standard methodologies used for detecting Δ9-Tetrahydrocannabinol (THC) in the clinical laboratory. Recognizing the need for appropriate testing, this chapter will review differences between sample types (urine, serum, saliva, hair and sweat), issues related to the respective sample being tested, and the most appropriate analysis. The chapter concludes with the challenges and limitations of testing for cannabinoids and metabolites.