The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, led to unprecedented demands assigned to clinical diagnostic laboratories worldwide, forcing them to make significant changes to their regular workflow as they adapted to new diagnostic tests and sample volumes. Herein, we summarize the modifications/adaptation the laboratory had to exercise to cope with rapidly evolving situations in the current pandemic. In the first phase of the pandemic, the laboratory validated 2 reverse transcription polymerase chain reaction-based assays to test ∼1000 samples/day and rapidly modified procedures and validated various preanalytical and analytical steps to overcome the supply chain constraints that would have otherwise derailed testing efforts. Further, the pooling strategy was validated for wide-scale population screening using nasopharyngeal swab samples and saliva samples. The translational research arm of the laboratory pursued several initiatives to understand the variable clinical manifestations that this virus presented in the population. The phylogenetic evolution of the virus was investigated using next-generation sequencing technology. The laboratory has initiated the formation of a consortium that includes groups investigating genomes at the level of large structural variants, using genome optical mapping via this collaborative global effort. This article summarizes our journey as the laboratory has sought to adapt and continue to positively contribute to the unprecedented demands and challenges of this rapidly evolving pandemic.