Personalized cancer therapy utilizes the patient's genotype and molecular characteristics of the tumor to identify the most effective cancer management for each patient. By tailoring therapy to the molecular vulnerabilities of a specific tumor, personalized cancer therapy aims to avoid the selection of less beneficial therapies, and thus may ultimately decrease costs and toxicity. The objective is to synthesize information about the tumor-its DNA, RNA, proteins, and metabolism to inform treatment decisions. Multiplex technologies to characterize tumors are becoming increasingly available. Approaches to use this information for optimal patient care are still evolving. In this chapter, we review approaches for molecular characterization, approaches to biomarker-driven trials, and barriers to implementation of personalized cancer therapy.