This chapter outlines the overarching methodological considerations and limitations which need to be considered in both epidemiology and molecular epidemiology studies. It aims to provide sufficient context for a diverse readership to be able to access the rest of the textbook. The chapter covers basic scientific concepts and principles, which will be expounded and built upon in subsequent chapters. Following on from the Introduction, this chapter introduces the reader to the broad range of disciplines encompassed by the field of molecular epidemiology, the applications of molecular epidemiology with real-world examples, and describes the rapid emergence and continued expansion of this scientific field. It highlights how the value of molecular epidemiology as a scientific discipline became increasingly clear during the COVID-19 pandemic. The chapter outlines some of the core concepts underpinning basic cell biology and microbial genomes, in addition to basic epidemiological concepts, such as study design, as well as their associated strengths and limitations. It goes on to discuss the methodological, epidemiological and statistical considerations which may impact the interpretation of molecular epidemiological studies. While both epidemiological and molecular epidemiological studies may share many limitations, they are also associated with their own unique limitations. The chapter includes a section on metrology which reviews the basic concepts of measurement science. Lastly, it concludes by highlighting the utility of both traditional and molecular epidemiological methods and how, in combination, their value can be synergistic.