With the launch of the National Cancer Institute's Precision Medicine Initiative in 2015, there has been a shift to trial designs that tailor health care solutions to individual patients by using a screening platform and by moving away from the one-trial/one-biomarker-at-a-time approach. To make precision medicine a reality, it is critical to identify and validate potential biomarkers to help select patients who will truly benefit from a targeted therapy. In this article, we discuss five trial designs: enrichment, umbrella, basket, subgroup, and window of opportunity. For each trial design, we describe the design characteristics, use ongoing or completed trials as case studies, provide any recent advances to the trial design, and discuss advantages and disadvantages of each design.