Drying is a commonly used technique for improving the product stability of biotherapeutics. Typically, drying is accomplished through freeze-drying, as evidenced by the availability of several lyophilized products on the market. There are, however, a number of drawbacks to lyophilization, including the lengthy process time required for drying, low energy efficiency, high cost of purchasing and maintaining the equipment, and sensitivity of the product to freezing and various other processing-related stresses. These limitations have led to the search for next-generation drying methods that can be applied to biotherapeutics. Several alternative drying methods are reviewed herein, with particular emphasis on methods that are commonly employed outside of the biopharmaceutical industry including spray drying, convective drying, vacuum drying, microwave drying, and combinations thereof. Although some of the technologies have already been implemented for processing biotherapeutics, others are still at an early stage of feasibility assessment. An overview of each method is presented, detailing the comparison to lyophilization, examining the advantages and disadvantages of each technology, and evaluating the potential of each to be utilized for drying biotherapeutic products. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2673–2695, 2014