The introduction of the new generation of particle-filled and high strength ceramics, hybrid composites and technopolymers in the last decade has offered an extensive palette of dental materials broadening the clinical indications in fixed prosthodontics, in the light of minimally invasive dentistry dictates. Moreover, last years have seen a dramatic increase in the patients’ demand for non-metallic materials, sometimes induced by metal-phobia or alleged allergies. Therefore, the attention of scientific research has been progressively focusing on such materials, particularly on lithium disilicate and zirconia, in order to shed light on properties, indications and limitations of the new protagonists of the prosthetic scene. This article is aimed at providing a narrative review regarding the state-of-the-art in the field of these popular ceramic materials, as to their physical-chemical, mechanical and optical properties, as well as to the proper dental applications, by means of scientific literature analysis and with reference to the authors’ clinical experience. A huge amount of data, sometimes conflicting, is available today. Both in vitro and in vivo studies pointed out the outstanding peculiarities of lithium disilicate and zirconia: unparalleled optical and esthetic properties, together with high biocompatibility, high mechanical resistance, reduced thickness and favorable wear behavior have been increasingly orientating the clinicians’ choice toward such ceramics. The noticeable properties and versatility make lithium disilicate and zirconia materials of choice for modern prosthetic dentistry, requiring high esthetic and mechanical performances combined with a minimal invasive approach, so that the utilization of such metal-free ceramics has become more and more widespread over time.