Cancer treatment is rapidly evolving and demand for more than modest incremental efficacy gains in highly competitive markets is growing. Given the complexity of the multiple pathways and aberrant targets that lead to oncogenesis and drug resistance, drug developers are pursuing novel combination therapies as a route to realizing substantial efficacy over monotherapy. Oncology markets are becoming increasingly segmented and crowded, and payer pressures are intensifying as oncology drug costs continue to rise. In response, pharmaceutical companies are developing combination therapies with the potential to deliver multiple commercial opportunities, including protection of existing marketed assets, differentiation from their competitors, and the possibility for substantial price premiums. However, companies will face tough decisions and challenges on the road to gaining regulatory approval and ensuring widespread uptake and market access of their combination therapy. Not least, developing an appropriate pricing strategy will be central to developing a novel combination therapy.