This paper examines the biosemiotic approach to the study of life processes by fashioning a series of questions that any worthwhile semiotic study of life should ask. These questions can be understood simultaneously as: (1) questions that distinguish a semiotic biology from a non-semiotic (i.e., reductionist–physicalist) one; (2) questions that any student in biosemiotics should ask when doing a case study; and (3) still currently unanswered questions of biosemiotics. In addition, some examples of previously undertaken biosemiotic case studies are examined so as to suggest a broad picture of how such a biosemiotic approach to biology might be done.