Home cage monitoring (HCM) offers a transformative approach to understanding rodent behavior and physiology in biomedical research. This chapter reviews the most commonly used mouse and rat models in HCM. Mice, particularly the C57BL/6 inbred strain, dominate the field due to their genetic homogeneity, ease of breeding, and well-characterized genome. Despite their advantages, researchers must consider strain- (and substrain-) specific traits that can be either strengths or limitations of the model (such as susceptibility to diet-induced obesity, age-related hearing loss, retinal degeneration and visual impairment, and differences in locomotor and exploratory activity). HCM allows for the continuous monitoring of behaviors such as activity and feeding, providing insights into subtle phenotypes and genetic influences on behavior. Other mouse strains, including DBA/2, 129, BALB/c, and FVB/N, offer unique behavioral profiles useful for specific research applications. In rats, strains like the Long-Evans, Dark Agouti, and Spontaneously Hypertensive Rat (SHR) are highlighted for their relevance in cognitive, metabolic, and cardiovascular studies. This chapter underscores the importance of selecting appropriate strains for HCM studies, considering genetic background, behavioral traits, and experimental goals. The continuous, automated nature of HCM systems promises to advance our understanding of complex behaviors and physiological responses, paving the way for innovative approaches in biomedical research.