The development of efficient and sustainable chemical processes which use greener reagents and solvents, currently play an important role in current research. Methanol, a cheap and readily available resource from chemical industry, could be activated by transition metal catalysts. This review focuses in covering the recent five-years literature and provides a systematic summary of strategies for methanol activation and the use in organic chemistry. Based on these strategies, many new synthetic methods have been developed for methanol utilization as the C1 building block in methylation, hydromethylation, aminomethylation, formylation reactions, as well as the syntheses of urea derivatives and heterocycles. The achievements, synthetic applications, limitations, some advanced approaches, and future perspectives of the methanol activation methodologies have been described in this review.