Bioelectrochemical systems (BESs) hold great promise for sustainable production of energy and chemicals. This review addresses the factors that are essential for practical application of BESs. First, we compare benefits (value of products and cleaning of wastewater) with costs (capital and operational costs). Based on this, we analyze the maximum internal resistance (in mΩ m2) and current density that is required to make microbial fuel cells (MFCs) and hydrogen-producing microbial electrolysis cells (MECs) cost effective. We compare these maximum resistances to reported internal resistances and current densities with special focus on cathodic resistances. Whereas the current densities of MFCs still need to be increased considerably (i.e., internal resistance needs to be decreased), MECs are closer to application as their current densities can be increased by increasing the applied voltage. For MFCs, the production of high-value products in combination with electricity production and wastewater treatment is a promising route.