Dendritic cell-associated C-type lectin-1 (Dectin-1), also known as β-glucan receptor is an emerging pattern recognition receptor (PRR) which belongs to the family of C-type lectin receptor (CLR). This CLR identifies ligands independently of Ca and is majorly involved in coupling of innate with adaptive immunity. Formerly, Dectin-1 was best known for its role in anti-fungal defense only. However, recent explorations suggested its wider role in defense against variety of infectious diseases caused by pathogens including bacteria, parasites and viruses. In fact, Dectin-1 signaling axis has been suggested to be targeted as an effective therapeutic strategy for cancers. Dectin-1 has also been elucidated ascetically in the heart, respiratory, intestinal, neurological and developmental disorders. Being a defensive PRR, Dectin-1 results in optimal immune responses in collaboration with other PRRs, but the overall evaluation reinforces the hypothesis of disease development on dis-regulation of Dectin-1 activity. This underscores the impact of Dectin-1 polymorphisms in modulating protein expression and generation of non-optimal immune responses through defective collaborations, further underlining their therapeutic potential. To add on, Dectin-1 influence autoimmunity and severe inflammation accredited to recognition of self T cells and apoptotic cells through unknown ligands. Few reports have also testified its redundant role in infections, which makes it a complicated molecule to be fully resolved. Thus, Dectin-1 is a hub that runs a complex collaborative network, whose interactive wire connections to different PRRs are still pending to be revealed. Alternatively, so far focus of almost all the researchers was the two major cell surface isoforms of Dectin-1, despite the fact that its soluble functional intracellular isoform (Dectin-1E) has already been dissected but is indefinable. Therefore, this review intensely recommends the need of future research to resolve the un-resolved and treasure the comprehensive role of Dectin-1 in different clinical outcomes, before determining its therapeutic prospective.