The last two decades have witnessed remarkable advance in our understanding the role of d‐amino acids in the mammalian nervous system: from the unknown, to known molecules with unknown functions, to potential central players in health and disease. d‐Amino acids have emerged as an important class of signaling molecules. In particular, the exploration of the roles of d‐serine in brain physiopathology is a vibrant field that is growing at an accelerating pace. However, disentangling the functions of a chiral molecule in a complex chemical matrice as the brain requires specific measurement and detection methods but is also a challenging task as many molecular tools and models investigators are using can lead to confounded observations. Thus, study of d‐amino acids demands accurate methodologies and specific controls, and these have often been lacking. Here we outline best practices for d‐amino acid research, with a special emphasis on d‐serine. We hope these concepts help move the field to greater rigor and reproducibility, allowing the field to advance.