Normal aging and aging-associated diseases, such as Alzheimer’s disease (AD), are complex processes influenced by various genetic and non-genetic factors, including diet, lifestyle, and socioeconomic status. While previous genome-wide association studies have implicated multiple genetic variants in aging and AD, there is a significant individual heterogeneity that cannot be explained by genetics alone. Epigenetic modifications, such as cytosine modifications (DNA methylation and hydroxymethylation) and RNA modifications, are significant contributors to gene regulation underlying normal biological processes and disease pathobiology. Technical advances have enabled the interrogation of epigenome-wide features using clinical biospecimens, including tissues, cells, and liquid biopsies. To date the most investigated epigenetic modifications for aging and aging-associated diseases, including AD, are 5-methylcytosines (5mC), which are known to primarily suppress gene expression. More recently, other important cytosine modifications, particularly 5-hydroxymethylcytosines (5hmC), have been implicated in various biological processes and diseases as well. Besides epigenetic modifications of cytosines on DNA, RNA modifications, specifically N6-Methyladenosine (m6A) modifications on mRNA molecules, have emerged as critical gene regulators with importance in determining disease development. In this chapter, we review current advances in the epigenetic contributions to normative aging and neurodegenerative diseases, focusing primarily on AD and related technological advances. Although the majority of the current research in this area has been on 5mC, the expansion of more recent research to such epigenetic modifications as 5hmC and m6A will greatly enhance our understanding of normative aging and aging-associated diseases, improve biomarker discovery, and lay the foundation for individualized prevention and treatment.