Driven by the ambitious goals of genome-related research, fully integrated microfluidic systems have developed rapidly to advance biomolecular and, in particular, genetic analysis. To produce a microsystem with high performance, several key elements must be strategically chosen, including device materials, temperature control, microfluidic control, and sample/product transport integration. We review several significant examples of microfluidic integration in DNA sequencing, gene expression analysis, pathogen detection, and forensic short tandem repeat typing. The advantages of high speed, increased sensitivity, and enhanced reliability enable these integrated microsystems to address bioanalytical challenges such as single-copy DNA sequencing, single-cell gene expression analysis, pathogen detection, and forensic identification of humans in formats that enable large-scale and point-of-analysis applications.