This work provides a unified theory that addresses the important problem of the origin and maintenance of genetic variation in natural populations. With modern molecular techniques, variation is found in all species, sometimes at astonishingly high levels. Yet, despite these observations, the forces that maintain variation within and between species have been difficult subjects of study. Because they act very weakly and operate over vast time scales, scientists must rely on indirect inferences and speculative mathematical models. However, despite these obstacles, many advances have been made. The author's research in molecular genetics, evolution, and bio-mathematics has enabled him to draw on this work, and present a coherent and valuable view of the field. The book is divided into three parts. The first consists of three chapters on protein evolution, DNA evolution, and molecular mechanisms. This section reviews the experimental observations on genetic variation. The second part gives a unified treatment of the mathematical theory of selection in a fluctuating environment. The final two chapters combine the earlier assessments in a treatment of the scientific status of two competing theories for the maintenance of genetic variation. Steeped in the enormous advances population genetics has made over the past 25 years, this book will be of interest to human geneticists, biologists, evolutionary theorists, and bio-mathematicians.