All living organisms conserve energy by catalyzing redox biochemical reactions, which constitute respiration. In most cases, respiration is achieved through the action of metalloenzymes and electron-transfer networks, wherein oxidation of reduced substrates is coupled to reduction of cofactors that pass along the electrons to a terminal oxidant. The latter is O2 in aerobic respiration and eukaryotes have no respiratory flexibility at the level of O2 reduction, for they can only use a single cytochrome oxidase. Conversely, bacteria and archaea incorporate highly branched respiratory chains where a plethora of molecules are used as terminal electron acceptors, including elemental sulfur, nitrogen oxides, transition metals, and radionuclides. Regardless, the free energy released during the electron transfer process drives proton translocation across the cell membrane, generating an electrochemical gradient (or proton motive force, PMF) that drives ATP synthesis. Despite these seminal advances, our understanding of energy conservation mechanisms is rather limited and key questions remain unanswered: (1) What is the true limit of respiratory flexibility? (2) Are organisms we consider to be “strict” anaerobes capable of evolving strategies for transitioning to an aerobic or microaerobic lifestyle? (3) How do bacteria thrive during long periods of energy starvation? I will elaborate on our recent work that offers insights into microbial innovations at the extremes of life.