Since its conception as an applied biomedical technology nearly 30 years ago, nanopore is emerging as a promising, high-throughput, biomarker-targeted diagnostic tool for clinicians. The attraction of a nanopore-based detection system is its simple, inexpensive, robust, user-friendly, high-throughput blueprint with minimal sample preparation needed prior to analysis. The goal of clinical-based nanopore biosensing is to go from sample acquisition to a meaningful readout quickly. The most extensive work in nanopore applications has been targeted at DNA, RNA, and peptide identification. Although, biosensing of pathological biomarkers, which is covered in this review, is on the rise. This review is broken into two major sections: (i) the current state of existing biological, solid state, and hybrid nanopore systems and (ii) the applications of nanopore biosensors toward detecting neurodegenerative biomarkers.