RNA interference (RNAi) is a powerful gene-silencing mechanism that has shown promise in therapeutic applications. However, the effective delivery of small interfering RNA (siRNA) to target cells remains a major challenge. This review discusses recent advances in siRNA delivery, focusing on synthetic materials that can encapsulate and deliver nucleic acids to cells. siRNA is a short RNA fragment that can specifically target and degrade complementary mRNA. The RNA-induced silencing complex (RISC) is responsible for the degradation of target mRNA. Despite the potential of RNAi, the delivery of siRNA to cells is hindered by factors such as degradation, immune response, and poor cellular uptake. To overcome these challenges, researchers have developed various synthetic delivery systems, including liposomes, polymers, and lipidoids. These materials can protect siRNA from degradation, enhance cellular uptake, and improve biodistribution. The review highlights the importance of chemical modifications to siRNA, such as 2'-O-methyl substitutions, to reduce immune activation and improve delivery. Additionally, the use of tissue-specific ligands in delivery systems can enhance targeting and biodistribution. The review also discusses the progress in clinical trials for RNAi-based therapies, including treatments for age-related macular degeneration and respiratory syncytial virus. Despite these advances, challenges remain in ensuring the safety and efficacy of RNAi therapeutics. Future research will focus on improving delivery systems and minimizing off-target effects to realize the full potential of RNAi in clinical applications.RNA interference (RNAi) is a powerful gene-silencing mechanism that has shown promise in therapeutic applications. However, the effective delivery of small interfering RNA (siRNA) to target cells remains a major challenge. This review discusses recent advances in siRNA delivery, focusing on synthetic materials that can encapsulate and deliver nucleic acids to cells. siRNA is a short RNA fragment that can specifically target and degrade complementary mRNA. The RNA-induced silencing complex (RISC) is responsible for the degradation of target mRNA. Despite the potential of RNAi, the delivery of siRNA to cells is hindered by factors such as degradation, immune response, and poor cellular uptake. To overcome these challenges, researchers have developed various synthetic delivery systems, including liposomes, polymers, and lipidoids. These materials can protect siRNA from degradation, enhance cellular uptake, and improve biodistribution. The review highlights the importance of chemical modifications to siRNA, such as 2'-O-methyl substitutions, to reduce immune activation and improve delivery. Additionally, the use of tissue-specific ligands in delivery systems can enhance targeting and biodistribution. The review also discusses the progress in clinical trials for RNAi-based therapies, including treatments for age-related macular degeneration and respiratory syncytial virus. Despite these advances, challenges remain in ensuring the safety and efficacy of RNAi therapeutics. Future research will focus on improving delivery systems and minimizing off-target effects to realize the full potential of RNAi in clinical applications.