One of the major emphases of the author's research program is to understand how obligate intracytoplasmic growth has affected the physiology of Rickettsia prowazekii. This chapter discusses metabolism and reductive evolution from the pathogenic rickettsia's point of view. Rapid advances in sequencing technologies have contributed to the ever-expanding availability of genome sequence information. This has significantly augmented our understanding of the factors that influence virulence and shape pathogen evolution at the genome level. The chapter summarizes the studies describing rickettsial physiology and metabolism before 1998, when the first rickettsial genome sequence became available. It provides insight into some of the key experiments that guided the field during a productive period in rickettsial research. The R.prowazekii adenosine triphosphate (ATP)/adenosine diphosphate (ADP) translocase is the best-characterized rickettsial transport system. It is well established that the ATP/ADP translocase functions via an obligate exchange antiport mechanism and thus requires the presence of substrate on both sides of the membrane to catalyze transport. Studies examining the physiology of rickettsiae that are growing intracellularly have contributed much to the understanding of rickettsia-host interactions. The chapter discusses how obligate intracellular growth has affected the rickettsia's capacity for gene regulation. As a final facet of rickettsial gene regulation, transcriptional termination is also explained in the chapter.