Many studies have highlighted the importance of the tight regulation of mRNA stability in the control of gene expression. mRNA stability largely depends on the mRNA nucleotide sequence, which affects the secondary and tertiary structures of the mRNAs, and the accessibility of various RNA-binding proteins to the mRNAs. Recent advances in high-throughput RNA-sequencing techniques have resulted in the elucidation of the important roles played by mRNA modifications and mRNA nucleotide sequences in regulating mRNA stability. To date, hundreds of different RNA modifications have been characterized. Among them, several RNA modifications, including N⁶-methyladenosine (m⁶A), N⁶,2′-O-dimethyladenosine (m⁶Am), 8-oxo-7,8-dihydroguanosine (8-oxoG), pseudouridine (Ψ), 5-methylcytidine (m⁵C), and N⁴-acetylcytidine (ac⁴C), have been shown to regulate mRNA stability, consequently affecting diverse cellular and biological processes. In this review, we discuss our current understanding of the molecular mechanisms underlying the regulation of mammalian mRNA stability by various RNA modifications.