We discuss the current practice of point-of-care diagnostics in infectious diseases as methods transition from antigen-based to molecular, and beyond simple molecular to the next generations of point-of-care testing methods. We evaluate the role of point-of-care at different sites of care and describe and evaluate trends likely to be driven by advances in molecular methodology, emerging biomarkers, and informatics. We describe strengths, weaknesses, opportunities, and threats to the development of point-of-care diagnostics in the near (1–10 years) and more distant (10–20 years) future.