Molecular diagnosis has become the gold standard for detecting infectious diseases, with its demand surging during the SARS-CoV-2 pandemic, particularly in regions with mandatory testing. These diagnostics primarily analyze nucleic acids, proteins, and biomolecular conjugates. For SARS-CoV-2, the focus was on detecting viral genes or their products, with nucleic acid testing (NAT), especially real-time polymerase chain reaction (RT-PCR), being the most widely used method. Rapid antigen and antibody tests were also employed but were secondary to reverse transcription-based techniques. The pandemic underscored the need for rapid, accurate, and scalable diagnostics to curb the spread of SARS-CoV-2. Time constraints occasionally necessitated alternative approaches like flow cell-based rapid tests or loop-mediated isothermal amplification (LAMP). Advances in genetic engineering, such as the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas system, have further revolutionized diagnostics by offering precise and efficient tools for genome targeting and disease detection. CRISPR’s guide RNA technology is now emerging as a promising next-generation diagnostic tool. The lessons learned from the COVID-19 pandemic have provided valuable insights for improving molecular diagnostic technologies. This chapter will explore various diagnostic approaches, including RT-PCR, LAMP, CRISPR, and rapid tests, while addressing the challenges and future prospects of these methods.