Ovarian cancer is a complex disease, with unclear origins, complicated, multistep tumorigenesis, and variable outcomes. As such, generating experimental models to study the disease and treatment efficacies has proven to be extremely challenging. A number of studies have utilized monolayer in vitro experiments to decipher the cellular changes in ovarian cancer and responses to different treatment approaches. Others have generated three-dimensional spheroid cultures to evaluate cellular function in an environment with more physiological contact with other cells and their matrices. Lastly, a variety of in vivo models have been used to investigate the onset and progression of ovarian cancer and how tumors respond to treatments in an intact physiological environment. This chapter discusses a number of different experimental approaches to study the etiology, biology, and pathology of ovarian tumors and their response to different anticancer therapies.