In physiology and life sciences, researchers rely on a wide range of signals to gather data from humans and animals. These signals provide critical insight into how complex organisms function under a myriad of conditions. However, this wealth of potential data sources can also present a challenge for researchers: choosing the right signals on which to focus their data gathering. For those lacking a background in the disciplines and mechanisms behind these signals, sifting through the available methodology can be overwhelming. The best place to begin is by considering one or a combination of the “Big Three” physiological signals: ECG, EDA, and respiration.