Laboratory models that accurately replicate human tumor initiation and characteristics are integral to advancing knowledge in cancer research. However, comparative studies between commonly employed laboratory models and human tumors have demonstrated that some models have molecular and genomic alterations dissimilar to the cancer type they attempt to replicate. In contrast, several recent comparative studies suggest that because patient-derived tumors grown in mice maintain many of the important characteristics of the original tumor, they represent an important tool for the development of new cancer therapeutics. Detailed in this overview are the advantages and disadvantages of the most commonly used cancer models for mechanistic and therapeutic research, with an emphasis on the advances made in the production and use of patient-derived tumorgrafts.