The renin-angiotensin system is essential for body fluid homeostasis and blood pressure regulation. This review focuses on the homeostatic regulation of the secretion of active renin in the kidney, primarily in humans. Under physiological conditions, renin secretion is determined mainly by sodium intake, but the specific pathways involved and the relations between them are not well defined. In animals, renin secretion is a log-linear function of sodium intake. Close associations exist between sodium intake, total body sodium, extracellular fluid volume, and blood volume. Plasma volume increases by about 1.5 mL/mmol increase in daily sodium intake. Several lines of evidence indicate that central blood volume may vary substantially without measurable changes in arterial blood pressure. At least five intertwining feedback loops of renin regulation are identifiable based on controlled variables (blood volume, arterial blood pressure), efferent pathways to the kidney (nervous, humoral), and pathways operating via the macula densa. Taken together, the available evidence favors the notion that under physiological conditions (1) volume-mediated regulation of renin secretion is the primary regulator, (2) macula densa mediated mechanisms play a substantial role as co-mediator although the controlled variables are not well defined so far, and (3) regulation via arterial blood pressure is the exception rather than the rule. Improved quantitative analyses based on in vivo and in silico models are warranted.