The development of biologics and small oral molecules has recently changed the scenario of pharmacologic treatment of systemic rheumatic diseases and it has become a real revolution. These drugs have innovative mechanisms of action, based on the inhibition of specific molecular or cellular targets directly involved in disease pathogenesis. This new scenario has lead to a regular update of the management recommendations of several institutions, such as those for Rheumatoid Arthritis treatment that address the use of conventional and biologic therapies including TNF inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, IL-6 inhibitors (tocilizumab and sarilumab), biosimilars and small oral molecules (the JAK inhibitors tofacitinib and baricitinib). Monotherapy, combination therapy, treatment strategies (such as treat-to-target) and the targets of sustained clinical remission or low disease activity are the final goal of the guidelines for rheumatic patients management. In another condition represented by Axial Spondyloarthritis guidelines suggest to start first with non-steroidal anti-inflammatory drugs to improve lifestyle and reduce spine inflammation, but if this is not achieved in 2-4 weeks it is important to consider the use of local therapies (i.e. glucocorticoid injections) or to start biologic therapy such as TNF inhibitors and then eventually switching to another TNF inhibitor or swapping to IL-17 inhibitor. In the case of active Psoriatic Arthritis, guidelines suggest to start with non-steroidal anti-inflammatory drugs and even local glucocorticoid injections especially for oligoarthritis, then to start conventional therapies if lack of efficacy, and finally start biologics or small oral molecules in the presence of drugs toxicity, unfavorable prognostic factors and still active arthritis. In several cases, active Psoriatic Arthritis patients develop a complex clinical condition with comorbidities such as diabetes, inflammatory bowel disease and high risk of infections, and for this reason the American College of Rheumatology and the National Psoriasis Foundation have developed specific guidelines for their management. Biologic and new small molecules therapies are very expensive, but the availability of biosimilars offers the opportunity of reducing the treatment cost and significantly decreasing the cost of originators as well. In fact, we live in a period characterized by the need to rationalize costs of these drugs, to allow treating a higher number of patients and to maintain a homogeneous possibility of treatment choice. For these reasons, we need to follow scientific guidelines and patients' clinical conditions to choose the correct treatment, also based on the economic burden of therapies.