I have the understanding that tcolorbox capabilities are a superset of mdframed. While mdframed tries to give you tools to create colorful frames, they look pale and simpler to me comparing to tcolorbox ones.
I think with enough tikz ninja skills you can achieve pretty much what you want with both, but somehow the tcolorbox syntax and options are simpler to me.
Also, tcolorbox has this "upper part/lower part" capabilities that mdframed lacks and creating a simple colored frame with a title seems simpler with tcolorbox.
From the documentation of mdframed
\mdfdefinestyle{theoremstyle}{%
linecolor=red,middlelinewidth=2pt,%
frametitlerule=true,%
apptotikzsetting={\tikzset{mdfframetitlebackground/.append style={%
shade,left color=white, right color=blue!20}}},
frametitlerulecolor=green!60,
frametitlerulewidth=1pt,
innertopmargin=\topskip,
}
\mdtheorem[style=theoremstyle]{definition}{Definition}
\begin{definition}[Inhomogeneous linear]
\ExampleText
\end{definition}
\begin{definition*}[Inhomogeneous linear]
\ExampleText
\end{definition*}

the equivalent in tcolorbox documentation:
\tcbuselibrary{theorems}
\newtcbtheorem[number within=section]{mytheo}{My Theorem}%
{colback=green!5,colframe=green!35!black,fonttitle=\bfseries}{th}
\begin{mytheo}{This is my title}{theoexample}
This is the text of the theorem. The counter is automatically assigned and,
in this example, prefixed with the section number. This theorem is numbered with
\ref{th:theoexample} and is given on page \pageref{th:theoexample}.
\end{mytheo}

@claudio-fiandrino mentioned that mdframe boxes can be customized with tikz. This is also the case with tcolorbox, since it relies on tikz.
\tcbset{colback=Salmon!50!white,colframe=FireBrick!75!black, width=(\linewidth-8mm)/2,before=,after=\hfill,equal height group=ske}
\begin{tcolorbox}[adjusted title=My title]
This is my content.
\end{tcolorbox}
\begin{tcolorbox}[skin=beamer,beamer,adjusted title=My title]
This is my content.
\end{tcolorbox}

tcolorboxis more advanced thanmdframed. My memory may bad though. Kindly excuse if I am wrong. – Oct 01 '13 at 02:05framedormdframed? (Pros/Cons) – cgnieder Oct 02 '13 at 08:54