The tomato (Solanum lycopersicum) Mi-1 gene encodes a protein with putative coiled-coil nucleotide-binding site and leucine-rich repeat motifs. Mi-1 confers resistance to root-knot nematodes (Meloidogyne spp.), potato aphids (Macrosiphum euphorbiae), and sweet potato whitefly (Bemisia tabaci). To identify genes required for the Mi-1-mediated or basal resistance to aphids, we used both genetic mutants and tobacco rattle virus-based virus (TRV)-induced gene silencing (VIGS) to repress candidate genes and assay for aphid resistance. Using the jai1-1 (jasmonic acid insensitive 1) tomato mutant in choice assays, the jai1-1 mutant showed higher colonization by potato aphids compared to wild-type tomato. In contrast, no-choice assays showed no difference in potato aphid survival or fecundity between jai1-1 and the wild-type parent. Plants homozygous for Mi-1 and for the jai1 mutation were not compromised in resistance to potato aphids using either choice or no-choice assays indicating no role of JA signaling in Mi-1 resistance to aphids. Using gene-specific VIGS, we silenced Sgt1, Rar1, and Hsp90-1, which are known to participate early in resistance gene signaling pathways. Silencing Sgt1 and Hsp90-1 indicated a role for these genes in Mi-1-mediated resistance. In contrast, silencing of Rar1 did not affect Mi-1-mediated aphid resistance, demonstrated that Rar1 is not required for Mi-1 resistance. In addition, using VIGS, several transcription factors and mitogen-activated protein kinase cascades required for Mi-1-mediated aphid resistance were identified. These results further demonstrate that resistance gene-mediated signaling events against piercing-sucking insects are similar to those against other plant pathogens.