In this Perspective, we have brought together available biological evidence on hydrazides as histone deacetylase inhibitors (HDACis) and as a distinct type of Zn-binding group (ZBG) to be reviewed for the first time in the literature. N-Alkyl hydrazides have transformed the field, providing innovative and practical chemical tools for selective and effective inhibition of specific histone deacetylase (HDAC) enzymes, in addition to the usual hydroxamic acid and o-aminoanilide ZBG-bearing HDACis. This has enabled efficient targeting of neurodegenerative diseases such as Alzheimer's disease, cancer, cardiovascular diseases, and protozoal pathologies.