Paper-based systems have been widely investigated for developing point-of-care devices because of their simplicity, affordability, and ease of use. Recent advances have resulted in paper systems that have progressed beyond the historical "single-strip" format and allow for a larger range of functions. This review provides a summary of the advances that have been made to improve the utility of paper-based diagnostic tests for biosensing. Specifically, techniques for designing paper devices, including different geometries and chemical patterning to control fluid flow, are discussed. This review also examines novel approaches to improve paper-based assay sensitivities, such as sample preconcentration, signal amplification at the detection zone, and electrochemical methods.