Enzyme-efficient states are metabolic states that realize a given flux objective at a minimal enzyme cost. Enzyme-efficient states can be hypothesized to be used under growth rate optimization regimes, as biomass production rate per enzyme can be converted to into cell growth rate. In models without further constraints, enzyme-efficient states are Elementary Flux Modes (EFMs). This allows for a algorithm to find enzyme-efficient states: Enumerate the EFMs, calculate the minimal enzyme cost per EFM, and choose the one with the lowest enzyme investment. This algorithm allows for finding of enzyme efficient states for larger models then can be optimized by 'brute force', but still need to be small enough to enumerate the EFMs. Such optimization has lead to the insights on the effect of changing external nutrient conditions: As growth conditions are changing, the optimal flux profile either changes continuously (and metabolite and enzyme concentrations change continuously as well) when the same EFM remains optimal, or fluxes change discontinuously together with metabolite and enzyme concentrations when a different EFM becomes optimal. Contributions: This chapter was planned and written by the authors and initially discussed with J. Zanghellini. The chapter was reviewed by D.S. Tourigny and H. Dourado and discussed with S. Müller.