Three scientific approaches to infectious disease-case series, epidemiologic investigation, and molecular analysis-have aided researchers in understanding the evolution of pathogen activity. Four eras of pathogen activity have occurred from 1920 to the present (streptococcus, staphylococci, gram-negative rods, and multidrug-resistant organisms). The emergence of health care-associated and community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) infections has resulted in the blurred distinction among the entities. In addition, there are several virulence factors that contribute significantly to the pathogenicity of the organism, and single nucleotide polymorphisms (SNPs) play an important role in determining an individual's response to infection. Health outcomes are significantly worse in MRSA patients compared with uninfected patients or those infected with methicillin-susceptible S. aureus (MSSA). Ongoing molecular research will continue to elucidate mechanisms associated with virulence of MRSA.