Life expectancy has always been associated to several determinants, such as environmental and genetic factors. Studies have related human lifespan as being 25-32 % due to genetic polymorphisms between individuals associated to longevity and aging. Nonetheless, no single gene will convey a phenotype like longevity. Aging is a process that occurs from changes in various levels of the cell, from genes to functions. Longevity is the ability to cope and repair the damage that results from these changes. It has been described as the result of an optimal performance of immune system and as an overexpression of anti-inflammatory sequence variants of immune/inflammatory genes.Longevity gene candidates can be separated into the following categories: inflammatory and immune-related, stress response elements, mediators of glucose and lipid metabolism, DNA repair components and cellular proliferation, and DNA haplogroups.Studies have related lifespan with Common Single-Nucleotide Polymorphisms (SNPs); polygenic effects can explain an important part of how genetics influence it. In this chapter we describe how to sequence Class I HLA allele polymorphism, as well as SNP sequencing, two methodologies most frequently used in polymorphism detection.