The development of new treatments for psoriasis provides dermatologists novel ways to help control the disease but raises questions about what laboratory screening tests are required. As of yet, no consensus or guidelines exist for dermatologists to follow and there may be misconceptions about the relative need for screening and monitoring tests in patients treated with biologic agents. Current practice ranges from no testing to blanket screening panels. The purposes of this review are to (1) systematically review the literature on the use of screening and monitoring tests when initiating and continuing biologic treatments (adalimumab, alefacept, efalizumab, etanercept, infliximab) for moderate to severe psoriasis or psoriatic arthritis; and (2) suggest practical guidelines for dermatologists on which to base such testing. We searched the Cochrane Collaborative Database (including the Cochrane Database of Systematic Reviews [Cochrane Reviews] and the Cochrane Central Register of Controlled Trials [Clinical Trials]) and the MEDLINE database using medical subject headings as search terms when available or key words when appropriate. We compiled published data on risk and risk assessment related to systemic psoriasis treatments, used expert opinion where appropriate when published clinical data were not adequately informative, and assigned evidence grades for various screening tests based on standard methods of the US Preventive Services Task Force. Finally, we developed a table of evidence grades for tests used to monitor different systemic medications. There is not strong evidence to recommend most screening tests for monitoring biological treatments. Neither is there strong evidence not to do such testing. Ultimately, from a practical standpoint, it is incumbent on the clinician to consider each patient independently and determine what screening tests are most appropriate for each individual patient.