In recent years there has been an abundance of research into the potential of helical peptides to influence cell function. These peptides have been used to achieve a variety of different outcomes from cell repair to cell death, depending upon the peptide sequence and the nature of its interactions with cell membranes and membrane proteins. In this critical review, we summarise several mechanisms by which helical peptides, acting as either transporters, inhibitors, agonists or antibiotics, can have significant effects on cell membranes and can radically affect the internal mechanisms of the cell. The various approaches to peptide design are discussed, including the role of naturally-occurring proteins in the design of these helical peptides and current breakthroughs in the use of non-natural (and therefore more stable) peptide scaffolds. Most importantly, the current successful applications of these peptides, and their potential uses in the field of medicine, are reviewed (131 references).