The question of complexity in biological systems is recurrent in evolutionary biology and is central in complex systems science for obvious reasons. But this question is surprisingly overlooked by Evolutionary Systems Biology. This comes unexpected given the roots of systems biology in complex systems science but also given that a proper understanding of the origin and evolution of complexity would provide clues for a better understanding of extant biological systems. In this chapter we will explore the links between evolutionary systems biology and biological systems complexity, in terms of concepts, tools, and results. In particular, we will show how complex models can be used to explore this question and show that complexity can spontaneously accumulate even in simple conditions owing to a “complexity ratchet” fuelled by sign-epistasis.