The attention of scientific research has grown in recent years on how to achieve more early and accurate diagnosis of oral diseases, and to carry out more efficient management of them. In fact, this attention is due to several reasons. Above all, it is due to the fact that there is a noticeable increase in the diagnosed Head and Neck Cancers (HNCs) worldwide, and the impact of early diagnosis and efficient management is widely reported to be effective on the prevention of oral cancers and the improvement of the patients quality of life. Secondly, medically compromised patients are confronted daily in our dental practice, and achieving adequate management with new concepts and tailored treatment strategies may decrease the high risk of significant comorbidities. Additionally, the introduction of new therapies and drugs is growing more and more in the medical field, and there is an obvious need to study and report their possible collateral effects on the oral cavity and how to manage these effects. Since many of the new therapies and drugs in many circumstances show successful results for many critical diseases, there is a need to detect, prevent, and manage their collateral effect. This issue can be clearly shown in the case of some anti-resorptive drugs for the management of bone metastases and their reported collateral effect on the oral cavity called Medications-Related Osteonecrosis of the Jaws (MRONI)), and the same issue can be shown in the case of myeloablative conditioning regimens and Hematopoietic Stem Cell Transplantation (HSCT) for the management of oncology-hematologic patients and their reported collateral effect of mucositis. The idea of proposing this Special Issue was to give an opportunity for recent and relevant research that studies new concepts to help in the early diagnosis of oral diseases and that investigates new treatment modalities for different oral diseases and complications. In response to the call for this Special Issue, eight papers were submitted and five of them have been accepted and published. Two papers studied concepts for the diagnosis of oral cancer [1, 2]. In the study by [PERSON] et al. [1], immune cell populations, including the qualitative and quantitative immunohistochemical analyses, were assessed in sixteen samples of squamous precancerous (preinvasive) and twenty-five samples of cancerous lesions obtained from the oral cavity and larynx of forty-one patients. The analysis revealed the presence of differences in the immunohistochemical profile between preinvasive and invasive squamous cell lesions without significance statistically. Therefore, the authors suggested, in conclusion, carrying out further studies on larger series of patients focusing on site-specific lesions due to the possible presence of usefulness of this investigation in driving the treatment strategy in both preinvasive and invasive squamous cell lesions of the oral cavity and larynx. The second paper was studied retrospectively the correlation between Oral Squamous Cell Carcinoma (OSCC) and some reported risk factors; including tobacco, alcohol, and Family History of Cancer (FHC) [2]. These risk factors were assessed on 239 patients with a confirmed diagnosis of OSCC (Test group) and 239 patients without history and/or diagnosis of oral cancer (Control group). The study revealed that patients with a high rate of tobacco consumption and drinker patients showed a significant risk of developing OSCC. For the FHC, the General Family History of Cancer (GFHC) showed a marginal risk and the Family History of Head and Neck Cancer (FHHNC) showed a notable risk without statistical significance. Based on this experience, the authors confirmed the possible presence of an association between alcohol and tobacco as risk factors and the OSCC. Additionally, they proposed the need for further evaluation of the GFHC and FHHNC as risk factors of the OSCC. The other three papers were investigating the effectiveness of different treatment modalities of different oral diseases [3; 4; 5]. In the paper by [PERSON] et al.