Modern biomedical sensing techniques have significantly increased in precision and accuracy due to new technologies that enable speed and that can be tailored to be highly specific for markers of a particular disease. Diagnosing early-stage conditions is paramount to treating serious diseases. Usually, in the early stages of the disease, the number of specific biomarkers is very low and sometimes difficult to detect using classical diagnostic methods. Among detection methods, biosensors are currently attracting significant interest in medicine, for advantages such as easy operation, speed, and portability, with additional benefits of low costs and repeated reliable results. Single-molecule sensors such as nanopores that can detect biomolecules at low concentrations have the potential to become clinically relevant. As such, several applications have been introduced in this field for the detection of blood markers, nucleic acids, or proteins. The use of nanopores has yet to reach maturity for standardization as diagnostic techniques, however, they promise enormous potential, as progress is made into stabilizing nanopore structures, enhancing chemistries, and improving data collection and bioinformatic analysis. This review offers a new perspective on current biomolecule sensing techniques, based on various types of nanopores, challenges, and approaches toward implementation in clinical settings.