The number of patients diagnosed with diminished ovarian reserve at the onset of their fertility treatment is constantly growing. The delay in the understanding of the prevalence of the problem and ways to manage it stemmed from a lack of a consensus definition. In this chapter, we will discuss the evolution of the definitions of the condition and the development of ovarian reserve tests. We will also discuss the currently used measures to try and improve IVF outcome in these women with change of stimulation drug, dose, treatment protocol, and the addition of adjuvants. We will also review the challenges in attempting treatment of women with exhausted ovarian reserve that are diagnosed with premature ovarian insufficiency. Lastly, we will try to gaze into the future and discuss promising interventions and medications designed to prevent loss of ovarian reserve.