The use of model systems is of obvious importance for understanding human physiology and pathophysiology However, the value of using human models for drug development has only relatively recently been appreciated An FDA review of drug development reported that 80% to 90% of drug candidates entering phase I clinical trials fail, with the most common causes of failure being lack of efficacy and toxicity Herein, recent advances in primary human culture models, their utility as preclinical testing platforms for drug target validation, and their importance in the future of drug discovery will be discussed