Combination therapies have shown great success in recent oncology drug development programs, including combination of immuno-therapies in NSCLC, and melanoma. There are multiple approaches to developing combination therapies. The number of combinations with immunotherapy is expanding but the patient resource is scarce. The challenge lies in finding the optimal dose combination that provides acceptable toxicity profile with increased efficacy. This talk with cover some of the common approaches used in clinical trials in the setting of the combination therapies. The different considerations that need to be considered when designing such a trial will be discussed. Some of the shortcomings of trials that use rule based methods will be discussed and alternatives in terms of model based methods will be presented. Trial designs used in dose finding of combination therapy will be critiqued with examples.