Interestingly, the core negative feedback motif is augmented with positive feedback loops in several of these systems. This raises the question of the evolutionary purpose of these auxiliary positive feedback loops. Tsai et al. have suggested that positive feedback loops provide robustness and tunability to oscillations in the system without elaborating on the kinetic mechanism by which such positive feedbacks are beneficial. In this work, we address the principles by which these positive feedback loops are beneficial in biochemical oscillations and unify several common mechanisms known to promote oscillations, such as Michaelis-Menten degradation kinetics and self-activation. We use a minimal well-studied formulation of this Presatovir threecomponent negative-feedback loop motif called the ��Goodwin oscillator�� for this (R)-(+)-BAY K 8644 theoretical study. The delay provided by three biochemical steps and cooperativity in the negative-feedback are essential for oscillations. This cooperativity can result from cooperative binding, allostery, reversible covalent modification or sequestration. Cooperativity is also intimately related to ��ultrasensitivity�� and ��nonlinearity�� in the biological modeling literature. The degree of cooperativity in the feedback is measured by the Hill coefficient; the larger the value of the coefficient, the higher the degree of cooperativity. One long-recognized limitation of this negative feedback only motif is the need for a high degree of cooperativity to produce oscillations. The complexity involved in evolving such high degrees of cooperativity is unknown and experimentally-measured Hill coefficients are in the range 2�C4. Nevertheless, mechanisms have been suggested that are theoretically capable of producing effectively high degrees of cooperativity, such as covalent modification and sequestration. Extending the length of the loop with additional steps is another way to alleviate the high degree of cooperativity required. In this work, we show that positive feedback loops provide a powerful alternative way of reducing these requirements, irrespective of the mechanism effecting this positive feedback.