In most species the functional activity of the mammary gland during lactation follows a biphasic developmental pattern. This pattern starts with a rapid increase in milk output that occurs with secretory activation and continues with a more gradual increase until the point of peak lactation is reached. Following this gain-of-function phase, the ability of the gland to produce milk decreases. This decrease occurs even if the lactation is prolonged by the presence of continued suckling stimulus and complete milk removal. This review describes the current state of our knowledge concerning the factors that regulate milk synthesis capacity by the mammary gland during the lactation cycle. The review describes four potential alternatives as mechanisms governing the process, which we refer to as secretory diminution. These alternatives are not presented as mutually exclusive of each other or other possible mechanisms, but are proposed as potential contributing mechanisms.