Senescent cells are highly associated with aging and pathological conditions and could be targeted to slow the aging process. One commonly used marker to examine senescent cells in vivo is p16, which has led to important discoveries. Recent studies have also described new senescence markers beyond p16 and have highlighted the importance of investigating senescence heterogeneity in cell types and tissues. With the development of high-throughput technologies, such as single-cell RNA-seq and single-nucleus RNA-seq, we can examine senescent cells at the single-cell level and potentially uncover new markers. This review emphasizes that there is an urgent need to investigate senescence heterogeneity and discuss how this could be accomplished by using advanced technologies and sequencing datasets. Currently, senescent cells do not have a known gold standard genetic marker.Single cell RNA-seq and single-nucleus RNA-seq have emerged as powerful methods for investigating senescence heterogeneity.It is unknown what cell populations are being targeted by senolytics in vivo.Gaining a greater understanding of senescent cell heterogeneity can have large clinical implications and improve patient treatment.