The various Cas proteins, combined with other technologies such as biosensors, biochips, biomagnetic beads, isothermal amplification, lateral flow, protein aptamers, etc. have led to the development of new molecular diagnostic methods with high sensitivity, specificity, low cost, short turnaround time, and portability in complex biological specimens. Most current CRISPR/Cas mediated diagnostic assays utilize Class 2 CRISPR/Cas systems that consist of type II (Cas9), type V (Cas12 and Cas14), and type VI (Cas13) CRISPR/Cas systems employing single multidomain effectors. Class 1 type I CRISPR/Cas3 system is also emerging for nucleic acid detection. The CRISPR/Cas12a, CRISPR/Cas13a, CRISPR/Cas14a and CRISPR/Cas3 systems depend on the measurement of trans-cleavage activity triggered by target sequence recognition 298, 299 (Figure ) trans-cleavage activity may be inhibited or nonspecifically activated by target-independent factors. The CRISPR/Cas9 system possesses excellent DNA recognition capability but does not possess trans-cleavage activity, and has been developed for biosensor-based diagnostics for its excellent DNA recognition capability. Only the CRISPR/Cas12a and CRISPR/Cas9 systems are available for dsDNA recognition. In this section, we have discussed the publication landscape of CRISPR-based disease diagnostics and briefly described their mechanisms.