In the era of novel biological agents, multiple myeloma (MM) is often approached as a chronic condition. While survival continues to improve, population-level data indicate that early mortality remains a substantial barrier to advances in MM outcomes. Here we provide "do's and don'ts" management recommendations that may minimize the risk of early mortality and ensure that patients have the opportunity to benefit from the long term impact of new effective MM agents. Such recommendations encompass the early introduction of novel agents even in the presence of comorbidities and advanced age and aggressive management of MM-related complications. Am. J. Hematol. 91:101-108, 2016.