The origin of chiral asymmetry in biology has attracted the attention of the research community throughout the years. In this paper we discuss the role of chirality and chirality sign alternation (L-D-L-D in proteins and D-L-D-L in DNA) in promoting self-organization in biology, starting at the level of single molecules and continuing to the level of supramolecular assemblies. In addition, we also discuss chiral assemblies in solutions of homochiral organic molecules. Sign-alternating chiral hierarchies created by proteins and nucleic acids are suggested to create the structural basis for the existence of selected mechanical degrees of freedom required for conformational dynamics in enzymes and macromolecular machines. Author Contributions: Conceptualization, V.A.T.; investigation, E.V.M.; writing-original draft preparation, V.A.T. and E.V.M. All authors have read and agreed to the published version of the manuscript.