Next-generation sequencing (NGS) applications have been transitioning from research tools to diagnostic methods and are becoming more commonplace in clinical microbiology laboratories. These applications include (1) whole-genome sequencing, (2) targeted next-generation sequencing methods, and (3) metagenomic next-generation sequencing. The introduction of these methods into the clinical microbiology laboratory has led to the theoretic question of “Will NGS-based methods supplant traditional methods for strain typing, identification, and antimicrobial susceptibility prediction?” The authors address this question and discuss where we are at now with clinical NGS applications for infectious diseases, what does the future hold, and at what cost?