Over the last years, evidence has suggested that phosphoinositides, which are involved in the regulation of a large variety of cellular processes both in the cytoplasm and in the plasma membrane, are present also within the nucleus. A number of advances has resulted in the discovery that phosphoinositide-specific phospholipase C signalling in the nucleus is involved in cell growth and differentiation. Remarkably, the nuclear inositide metabolism is regulated independently from that present elsewhere in the cell. Even though nuclear inositol lipids hydrolysis generates second messengers such as diacylglycerol and inositol 1,4,5-trisphosphate, it is becoming increasingly clear that in the nucleus polyphosphoinositides may act by themselves to influence pre-mRNA splicing and chromatin structure. Among phosphoinositide-specific phospholipase C, the beta(1) isoform appears to be one of the key players of the nuclear lipid signaling. This review aims at highlighting the most significant and up-dated findings about phosphoinositide-specific phospholipase C beta(1) in the nucleus.