This review discusses nutrient sensing mechanisms and pathways in mammals, focusing on glucose, amino acids, and lipids. Nutrient sensing is essential for life, enabling cells to respond to environmental fluctuations and maintain homeostasis. In mammals, nutrient sensing pathways regulate anabolism and storage during abundance, and homeostatic mechanisms like autophagy during scarcity. These pathways are often dysregulated in metabolic diseases. Lipid sensing involves G-protein coupled receptors like GPR40 and GPR120, which detect long-chain fatty acids and mediate insulin release. The cholesterol sensing mechanism, discovered by Brown and Goldstein, involves SCAP and SREBP proteins that regulate cholesterol biosynthesis. The FAT/CD36 receptor also plays a role in fatty acid uptake. Amino acid sensing includes GCN2, which detects uncharged tRNAs and initiates a signaling cascade to regulate translation. mTORC1 is a key regulator of nutrient sensing, integrating information on both systemic and cellular nutrient levels. Amino acid-sensing taste receptors, such as T1R1+T1R3, detect amino acids and influence nutrient intake. Glucose sensing involves GCK and GLUT2, which regulate glucose homeostasis. The glucose transporter GLUT2 acts as an extracellular glucose sensor, while GCK is an intracellular glucose sensor. Glucose-sensing taste receptors, like T1R2+T1R3, detect glucose and influence nutrient intake. Autophagy is a critical process for mobilizing internal nutrient stores during scarcity. It is regulated by mTORC1 and AMPK, which respond to nutrient levels and energy status. Autophagy is essential for cellular survival and is involved in various physiological processes, including embryonic development and organ function. The review highlights the complexity of nutrient sensing mechanisms and the challenges in understanding their integration. It emphasizes the importance of identifying nutrient sensors and understanding their interactions with other signaling pathways. Nutrient sensing is crucial for maintaining metabolic homeostasis and preventing diseases like diabetes and cancer. Understanding these mechanisms is essential for developing therapeutic strategies to combat metabolic disorders.This review discusses nutrient sensing mechanisms and pathways in mammals, focusing on glucose, amino acids, and lipids. Nutrient sensing is essential for life, enabling cells to respond to environmental fluctuations and maintain homeostasis. In mammals, nutrient sensing pathways regulate anabolism and storage during abundance, and homeostatic mechanisms like autophagy during scarcity. These pathways are often dysregulated in metabolic diseases. Lipid sensing involves G-protein coupled receptors like GPR40 and GPR120, which detect long-chain fatty acids and mediate insulin release. The cholesterol sensing mechanism, discovered by Brown and Goldstein, involves SCAP and SREBP proteins that regulate cholesterol biosynthesis. The FAT/CD36 receptor also plays a role in fatty acid uptake. Amino acid sensing includes GCN2, which detects uncharged tRNAs and initiates a signaling cascade to regulate translation. mTORC1 is a key regulator of nutrient sensing, integrating information on both systemic and cellular nutrient levels. Amino acid-sensing taste receptors, such as T1R1+T1R3, detect amino acids and influence nutrient intake. Glucose sensing involves GCK and GLUT2, which regulate glucose homeostasis. The glucose transporter GLUT2 acts as an extracellular glucose sensor, while GCK is an intracellular glucose sensor. Glucose-sensing taste receptors, like T1R2+T1R3, detect glucose and influence nutrient intake. Autophagy is a critical process for mobilizing internal nutrient stores during scarcity. It is regulated by mTORC1 and AMPK, which respond to nutrient levels and energy status. Autophagy is essential for cellular survival and is involved in various physiological processes, including embryonic development and organ function. The review highlights the complexity of nutrient sensing mechanisms and the challenges in understanding their integration. It emphasizes the importance of identifying nutrient sensors and understanding their interactions with other signaling pathways. Nutrient sensing is crucial for maintaining metabolic homeostasis and preventing diseases like diabetes and cancer. Understanding these mechanisms is essential for developing therapeutic strategies to combat metabolic disorders.