Transition from seed to seedling represents a critical stage in plants' life cycles. This process includes three significant events in the seeds: (i) tissue hydration, (ii) the mobilization of reserve nutrients, and (iii) the activation of metabolic activity. Global metabolic rearrangements lead to the initiation of radicle growth and the resumption of vegetative development. It requires massive reprogramming of the transcriptome, proteome, metabolome, and attendant signaling pathways, resulting in the silencing of seed-maturation genes and the activation of vegetative growth genes. This Special Issue discusses the mechanisms of genetic, epigenetic, and hormonal switches during seed-to-seedling transitions. Detailed information has also been covered regarding the influence of germination features on seedling establishment.