In recent years, expansion of unconventional oil and gas production has prompted significant interest in potential impacts on drinking water resources. In many cases, water quality investigations rely on access to landowner water wells to develop baseline data prior to drilling; respond to spills, complaints, or incidents; or evaluate potential impacts due to drilling, completion, hydraulic fracturing, water management, or well operation. However, differences in water well construction, operation, maintenance, and wellhead protection practices can complicate sampling efforts and introduce artifacts that might confound interpretation of results and definition of baseline conditions. The frequency of sampling and the types of analyses also vary from site to site, ranging from basic field parameters such as conductivity, pH, and water level to comprehensive analyses of organics, inorganics, radionuclides, gases, stable isotopes, and microorganisms. Regulatory agencies may also specify required analytical parameters and monitoring frequency. This paper highlights some of the challenges associated with deriving baseline data from different types of wells and provides preliminary data on the use of chemical fingerprinting to differentiate sources of waterborne contaminants.