Molecular diagnostics is critical for prevention, identification, and treatment of disease. Traditional technologies for molecular diagnostics using blood are limited to laboratory use because they rely on sample purification and sophisticated instruments, are labor- and time-intensive and expensive, and require highly trained operators. This review discusses the frontiers of point-of-care diagnostic technologies using a drop of blood obtained from a finger-prick. These technologies, including emerging biotechnologies, nanotechnologies, and microfluidics, hold the potential for rapid, accurate, and inexpensive disease diagnostics.