<p>Rice is a staple food for over half of the world's population. To feed the growing population, molecular breeders aim to increase grain yield. Grain size is an important factor for crop productivity, and it has been extensively studied. However, molecular breeders face a major challenge in further improving crop productivity in terms of grain yield and quality. Grain size is a complex trait controlled by multiple genes. Over the past few decades, genetic studies have identified various gene families involved in grain size development. The list of molecular mechanisms, and key regulators involved in grain size development is constantly expanding, making it difficult to understand the main regulators that play crucial roles in grain development. In this review, we focus on the major regulators of grain size, including G-protein signaling, the mitogen-activated protein kinase (MAPK) pathway, transcriptional regulation, the ubiquitin–proteasome degradation (UPD) pathway, and phytohormone signaling. These molecular mechanisms directly or indirectly regulate grain size. We provided a comprehensive understanding of the genes involved in these mechanisms and cross discussions about how these mechanisms are interlinked. This review serves as a valuable resource for understanding the molecular mechanisms that govern grain development and can aid in the development of molecular breeding strategies.</p>