Serotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine involved in neurotransmission, peripheral hormone function, and mitogenesis. It plays a critical role in the central nervous system (CNS) and gastrointestinal (GI) tract, with diverse functions including GI motility, vasoconstriction, angiogenesis, and immune modulation. Recent research has highlighted the complex role of serotonin in cancer pathogenesis, revealing both pro-tumorigenic and anti-tumorigenic effects. The serotonergic system, including serotonin receptors (5-HT receptors), serotonin transporter (SERT), and serotonin synthesis enzymes, is involved in various cancer-related processes, such as cell proliferation, apoptosis, and immune modulation. The biosynthesis of 5-HT involves the conversion of L-tryptophan to 5-HT through tryptophan hydroxylase (TPH) and aromatic amino acid decarboxylase. 5-HT is stored in presynaptic neurons and released into the synaptic cleft, where it binds to 5-HT receptors (5-HTRs), triggering various intracellular signaling pathways. These pathways include G-protein-coupled receptor (GPCR) signaling, ligand-gated ion channels, and receptor-independent mechanisms such as serotonylation. 5-HT has been implicated in the progression of various cancers, including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), breast cancer (BC), and melanoma. It promotes tumor growth, inhibits apoptosis, and enhances angiogenesis through various 5-HTRs. Additionally, serotonin signaling can modulate the tumor microenvironment (TME), influencing immune cell function and promoting immune evasion. Serotonin also plays a role in angiogenesis, with 5-HT activating signaling pathways such as PI3K-AKT-mTOR and Wnt/β-catenin, which are critical for tumor progression. The serotonergic system is involved in immune modulation, with serotonin affecting the function of macrophages, dendritic cells, and T cells. Serotonin can enhance antitumor immunity by promoting the differentiation of regulatory T cells (Tregs) and suppressing pro-inflammatory responses. Serotonin receptor-directed therapies, including 5-HT receptor antagonists and agonists, have shown potential in cancer treatment. Selective serotonin reuptake inhibitors (SSRIs) have been evaluated for their antitumor effects, with some studies indicating a reduced risk of certain cancers, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). SSRIs may also enhance the efficacy of other cancer treatments by modulating signaling pathways involved in tumor growth and survival. In summary, serotonin signaling is a complex and multifaceted process that influences various aspects of cancer biology, including cell proliferation, apoptosis, angiogenesis, and immune modulation. The serotonergic system presents promising therapeutic opportunities for cancerSerotonin (5-hydroxytryptamine, 5-HT) is a multifunctional bioamine involved in neurotransmission, peripheral hormone function, and mitogenesis. It plays a critical role in the central nervous system (CNS) and gastrointestinal (GI) tract, with diverse functions including GI motility, vasoconstriction, angiogenesis, and immune modulation. Recent research has highlighted the complex role of serotonin in cancer pathogenesis, revealing both pro-tumorigenic and anti-tumorigenic effects. The serotonergic system, including serotonin receptors (5-HT receptors), serotonin transporter (SERT), and serotonin synthesis enzymes, is involved in various cancer-related processes, such as cell proliferation, apoptosis, and immune modulation. The biosynthesis of 5-HT involves the conversion of L-tryptophan to 5-HT through tryptophan hydroxylase (TPH) and aromatic amino acid decarboxylase. 5-HT is stored in presynaptic neurons and released into the synaptic cleft, where it binds to 5-HT receptors (5-HTRs), triggering various intracellular signaling pathways. These pathways include G-protein-coupled receptor (GPCR) signaling, ligand-gated ion channels, and receptor-independent mechanisms such as serotonylation. 5-HT has been implicated in the progression of various cancers, including colorectal cancer (CRC), hepatocellular carcinoma (HCC), gastric cancer (GC), breast cancer (BC), and melanoma. It promotes tumor growth, inhibits apoptosis, and enhances angiogenesis through various 5-HTRs. Additionally, serotonin signaling can modulate the tumor microenvironment (TME), influencing immune cell function and promoting immune evasion. Serotonin also plays a role in angiogenesis, with 5-HT activating signaling pathways such as PI3K-AKT-mTOR and Wnt/β-catenin, which are critical for tumor progression. The serotonergic system is involved in immune modulation, with serotonin affecting the function of macrophages, dendritic cells, and T cells. Serotonin can enhance antitumor immunity by promoting the differentiation of regulatory T cells (Tregs) and suppressing pro-inflammatory responses. Serotonin receptor-directed therapies, including 5-HT receptor antagonists and agonists, have shown potential in cancer treatment. Selective serotonin reuptake inhibitors (SSRIs) have been evaluated for their antitumor effects, with some studies indicating a reduced risk of certain cancers, such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). SSRIs may also enhance the efficacy of other cancer treatments by modulating signaling pathways involved in tumor growth and survival. In summary, serotonin signaling is a complex and multifaceted process that influences various aspects of cancer biology, including cell proliferation, apoptosis, angiogenesis, and immune modulation. The serotonergic system presents promising therapeutic opportunities for cancer